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Adipose tissue derived stromal cells for the treatment of neurological disorders

a stromal cell and adipose tissue technology, applied in the direction of fused cells, skeletal/connective tissue cells, peptide/protein ingredients, etc., can solve the problems of brain cell death, brain damage irreversible, high risk and discomfort of bone marrow stromal cells, etc., and achieve the effect of reducing the functional defici

Inactive Publication Date: 2009-09-01
VETSTEM BIOPHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The treatment significantly reduces functional deficits in stroke and CNS injuries by promoting neurogenesis, angiogenesis, and tissue repair, offering a therapeutic benefit without inducing an immune response and potentially reducing the need for immunosuppressive agents.

Problems solved by technology

In the absence of treatment, these animals died because they failed to replenish their circulating blood cells; however, transplantation of bone marrow cells from syngeneic donor animals rescued the host animal.
However, extraction of bone marrow stromal cells presents a high level of risk and discomfort to the patient.
These injuries share the same common pathologic process of rapid cerebral edema leading to irreversible brain damage and eventually to brain cell death.
Stroke results in the destruction of brain tissue as a result of intracerebral hemorrhage or infarction.
Stroke may be caused by reduced blood flow or ischemia that results in deficient blood supply and death of tissues in one area of the brain (infarction).
The CNS tissue is highly dependent on blood supply and is very vulnerable to interruption of blood supply.
Even a brief interruption of the blood flow to the CNS can cause neurological deficit.
It has been observed that after blood flow is restored to areas of the brain that have suffered an ischemic injury, secondary hemodynamic disturbances have long lasting effects that interfere with the ability of the blood to supply oxygen to CNS tissues.
Similarly, interruption of the blood flow to the spinal cord, for even short periods of time, can result in paralysis.
Results of various trials have yielded disappointing efficacy data and some evidence of safety problems, including increased mortality or psychotic effects which resulted in the early termination of the trials.
Existing therapies rely on prompt treatment (i.e within minutes / hours) following a stroke but there is presently no effective or beneficial therapy that can be applied at later time points (days / weeks) after the onset of stroke.
Thus there remains a large unmet need for treatments that improve neurological function after the onset of stroke.

Method used

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  • Adipose tissue derived stromal cells for the treatment of neurological disorders
  • Adipose tissue derived stromal cells for the treatment of neurological disorders
  • Adipose tissue derived stromal cells for the treatment of neurological disorders

Examples

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example 1

Hematopoietic Commitment by Adipose Tissue-Derived Stromal Cells

[0133]A. Stromal cells are isolated from human adipose tissue according to the methods described in U.S. patent application Ser. No. 09 / 240,029, Filed Jan. 29, 1999, now U.S. Pat. No. 6,153,432 (the contents of which are incorporated by reference), and using the modifications to the growth medium as described above. Briefly, human preadipocytes were isolated from adipose tissue removed by liposuction surgery according to the procedures previously described by Rodbell and Hauner (Rodbell (1967) and (1974); Hauner, supra). Preadipocytes from the stromal-vascular fraction were resuspended in DMEM (high glucose) media containing 10% fetal bovine serum, 5% chick embryo extract, and antibiotics and plated at 25,000 cells / well in each of the wells of a 96 well plate (150 μl / well). The cells were then placed in a 37° C. 5% CO2 incubator and allowed to settle overnight. The cells are cultured as primary cultures for a period of ...

example 2

Astroglial Commitment by Human Adipose Tissue-Derived Stromal Cells

[0137]A. Stromal cells are isolated from human adipose tissue according to the methods described above. The cells are cultured as primary cultures for a period of up to 5 days following initial plating in a medium composed of, but not limited to, DMEM (high glucose) media containing 10% fetal bovine serum, 5% chick embryo extract, and antibiotics at 37° C. Cells are harvested by trypsin / EDTA digestion prior to differentiation / implantation.

[0138]Cells are transplanted into the central nervous system of immunodeficient mice or rats. Nude / beige or SCID mice or nude rats are anesthetized in a sealed chamber using 3% halothane in oxygen; anesthesia is maintained by intramuscular injection of 6 mg / kg of xylozine and 60 mg / kg of ketamine. The animals are transferred to a sterotaxic apparatus in a clean field. A 2-to-5-mm incision is made in the scalp 2 mm lateral to the bregma. A burr hole is made in the bone 3 mm lateral t...

example 3

Neuronal Commitment by Human Adipose Tissue-Derived Stromal Cells

[0141]Improved Repair and Functional Recovery in a Traumatic Nervous System Injury

[0142]Stromal cells are isolated from human adipose tissue of an individual patient for autologous or allogeneic transplantation to a histocompatible recipient according to the methods described above. The cells are cultured as primary cultures for a period of up to 5 days following initial plating in a medium composed of, but not limited to, DMEM (high glucose) media with 1 mM glutamine but without pyruvate, containing 10% fetal bovine serum, 10% newborn calf serum, nucleoside stocks, 0.1 mM 2-mercaptoethanol, 1000 units / ml of leukemia inhibitory factor and antibiotics at 37° C.

[0143]Cells are harvested by trypsin / EDTA digestion prior to differentiation / implantation. Cells are then plated on tissue culture plastic substrate coated with 0.1% sterile gelatin solution. Cells are harvested during rapid growth stage by 0.25% trypsin and 1 mM ...

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Abstract

The present invention relates to a treatment of neural injury and neurodegenerative diseases. Also included in the present invention is the use of adipose tissue derived stromal cells for the treatment of neural injury (stroke, traumatic brain injury, spinal cord injury) and neurodegeneration (i.e. Parkinson's disease).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation-in-part of U.S. patent application Ser. No. 09 / 793,173, filed on Feb. 26, 2001, which claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 60 / 185,338, filed Feb. 26, 2000, all of which are herein incorporated by reference in their entirety.BACKGROUND OF THE INVENTION[0002]A stem cell must meet the following criteria: (1) ability of a clonal stem cell population to self-renew; (2) ability of a clonal stem cell population to generate a new, terminally differentiated cell type in vitro; (3) ability of a clonal stem cell population to replace an absent terminally differentiated cell population when transplanted into an animal depleted of its own natural cells.[0003]The neonatal period in human development is characterized by the presence of “stem” cells with the potential to develop along multiple differentiation pathways. The terminal differentiation of these cells is deter...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A01N63/00C12N5/00C12N5/06C12N5/08C12N5/16A61K35/35C12N5/074C12N5/0775
CPCC12N5/0607A61K35/35C12N5/0667A61K38/00A61P25/00
Inventor WILKISON, WILLIAM O.GIMBLE, JEFFREY M.VANGURI, PADMAVATHY
Owner VETSTEM BIOPHARMA INC
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